EP0597785A1 - Verfahren zur Anregung und Ermittlung von magnetischen Kernresonanzsignalen, insbesondere in Leichtwasser - Google Patents

Verfahren zur Anregung und Ermittlung von magnetischen Kernresonanzsignalen, insbesondere in Leichtwasser Download PDF

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Publication number
EP0597785A1
EP0597785A1 EP93440090A EP93440090A EP0597785A1 EP 0597785 A1 EP0597785 A1 EP 0597785A1 EP 93440090 A EP93440090 A EP 93440090A EP 93440090 A EP93440090 A EP 93440090A EP 0597785 A1 EP0597785 A1 EP 0597785A1
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EP
European Patent Office
Prior art keywords
selective
pulsed
pulse
radiofrequency
pulses
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EP93440090A
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French (fr)
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EP0597785B1 (de
Inventor
Martial Piotto
Vladimir Sklenar
Vladimir Saudek
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Bruker SA
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Sadis Bruker Spectrospin SA
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/46—NMR spectroscopy
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/46—NMR spectroscopy
    • G01R33/4608—RF excitation sequences for enhanced detection, e.g. NOE, polarisation transfer, selection of a coherence transfer pathway

Definitions

  • the present invention relates to the field of methods and techniques related to the application of nuclear magnetic resonance (NMR), in particular for high resolution experiments, and relates to a method of excitation and acquisition of NMR signals. , especially in light water.
  • NMR nuclear magnetic resonance
  • Multidimensional NMR has become an essential instrument for studying molecules in solution, in particular biomolecules, and has proven itself as a valid alternative to X-ray crystallography.
  • a crucial step for the determination of these structures is the attribution of the signals of all the protons of the molecule to be analyzed and, in particular, of the protons in exchange with those of water or the corresponding solvent.
  • the proton concentration of water is 110 M (molars) while the solute concentration (molecules to be analyzed) is around 2 mM (millimolars).
  • a first category of methods and methods implements selective excitation sequences as a signal detection pulse, such as in particular the method known under the name "jump and return", described by P. Plateau and M. Guéron in the document J. Am. Chem. Soc., 104, 7310 (1982) or the process known under the name "11 - echo” described by V. Sklenar and A. Bax in the document J. Magn. Reson., 74, 469 (1987).
  • the various processes and methods grouped in the second category propose to phase the transverse component of the magnetization of water by an inhomogeneous radiofrequency field by means of a locking of spins (see BA Messerle, G. Wider, G. Wider, G. Otting, C. Weber and K. Wuthrich, J. Magn. Reson., 85, 608 - 1989).
  • the "jump and return" process can be implemented for one-dimensional or type NMR experiments known under the name NOESY (Nuclear Overhauser Effect Spectroscopy), but is very ineffective in combination with NMR experiments of the types known under the names TOCSY (TOtally Correlated Spectroscopy - and ROESY (ROtating Overhauser Effect Spectroscopy) and is practically not used for heteronuclear NMR experiments .
  • NOESY Nuclear Overhauser Effect Spectroscopy
  • HMQC Heteronuclear Multiple Quantum Coherence - multiple coherence heteronuclear quanta
  • HSQC Heteronuclear Single Quantum Coherence - simple coherence quanta heteronuclear
  • the methods and methods implementing the pulsed field gradient techniques are effective, for the suppression of the water peak, only in the context of NMR experiments of the heteronuclear type and are of no use in the NOESY, TOCSY and ROESY type experiments.
  • the present invention aims in particular to overcome all of the aforementioned drawbacks.
  • a method of excitation and acquisition of NMR signals in particular for the analysis of molecules dispersed in a solvent, such as for example water, characterized in that it consists essentially subjecting the sample to be analyzed first to a sequence of pulses corresponding to the high-resolution NMR experiment to be carried out, then applying a first pulsed field gradient in a given direction to it, then subjecting it to a selective pulsed radiofrequency field of 180 °, affecting the entire spectrum with the exception of the resonance frequency of the water or the corresponding solvent, applying a second pulsed field gradient, identical to the first and, finally, perform the acquisition and processing of the resulting NMR signals.
  • a solvent such as for example water
  • the method of excitation and acquisition of NMR signals essentially consists in first of all subjecting the sample to be analyzed to a sequence of pulses 1 corresponding to the high resolution NMR experiment to be carried out, then to apply a first pulsed field gradient 2 in a given direction, for example the Z direction, to then subject it to a selective pulsed radiofrequency field 3 of 180 °, affecting the entire spectrum except the resonance frequency of l water, applying a second pulsed field gradient 4 to it, identical to the first and, finally, carrying out the acquisition and processing of the resulting NMR signals.
  • the selective pulsed radiofrequency field 3 of 180 ° is therefore selectively applied to the protons to be analyzed in the context of the NMR experiment carried out, but does not affect the resonance of the solvent, for example preferably water.
  • the term “selective” designates a field or a pulse affecting the entire spectrum, except for the resonant frequency of the water or of the corresponding solvent and the term “non-selective” designates a field or a pulse affecting the entire spectrum without exception.
  • the pulsed field gradients 2 and 4 and the selective pulsed radio frequency field 3 of 180 ° are implemented immediately after completion of the corresponding pulse sequence to the NMR experience to be carried out.
  • the field gradients 2 and 4 and the application of the radiofrequency field 3 are inserted in the refocusing period of the so-called inverted INEPT step (Insensitive Nuclei Enhanced by Polarization Transfer - insensitive nuclei improved by polarization transfer).
  • the duration of the field gradients 2 and 4 and of the radiofrequency field 3 should be taken into account when adjusting the refocusing delay ( Figure 7).
  • the two pulsed field gradients 2 and 4 preferably have envelopes of sinusoidal pulses, making it possible to eliminate or to attenuate the signals corresponding to the water or to the solvent used, to a degree such that their intensity becomes comparable to that of the signals of the protons to be analyzed within the framework of the experiment carried out.
  • envelopes are also possible such as for example envelopes of the square, Gaussian or Lorentzian type.
  • the total time elapsing between the end of the NMR experiment carried out and the start of the acquisition of the resulting NMR signals is less than 6 milliseconds, taking into account the durations of recovery of the gradients of approximately 125 microseconds.
  • the 180 ° selective pulsed radiofrequency field 3 can be constituted by three successive components, namely, a non-selective 180 ° radiofrequency pulse 6 oriented in a given direction X, and two identical, low power, 7 ° and 7 'radio frequency pulses 90 °, one of which precedes and the other 7' of which follows the non-selective radio frequency pulse 6 of 180 °, being oriented in a direction -X opposite to the X direction of the latter ( Figure 1B).
  • the radiofrequency pulses 7 and 7 ′ selective at 90 ° can then consist, advantageously, either in rectangular pulses, or in amplitude-modulated pulses such that the amplitude variations liable to be introduced into the excitation profile are eliminated (FIG. 2A).
  • the width of the non-excited region is delimited by the length of said selective pulses 7 and 7' of 90 ° (length T) while the excitation bandwidth is limited mainly by the intensity of the radiofrequency field of the non-selective pulse 6 of 180 °.
  • the spectral domain exhibiting reduced intensities is limited to frequencies multiple of 1 / T from the frequency of the carrier centered on the spectral position corresponding to the resonance peak of water.
  • the amplitude variation introduced by the two rectangular pulses 7 and 7 ′ selective by 90 ° is less than 10% and can be eliminated by modulating the envelopes of these pulses 7 and 7 ′.
  • This high power pulse sequence can be obtained by optimization by means of a computer simulation and has optimal refocusing properties.
  • sequence of pulses of high power can also present the respective phases (0,180,0,0,180,0) for its various successive components, allowing the suppression of the spectral peak of resonance of water or solvent corresponding to frequencies offset by +/- (2k + 1) / 2 ⁇ with respect to the carrier frequency.
  • the two pulse sequences described above generate spectra composed of pure phase signals and achieve a significant suppression or attenuation of the peak corresponding to the water or the corresponding solvent, with an attenuation factor of the order of 104 to 105, during a single scan.
  • the pulsed field gradient 4 immediately preceding the acquisition phase ensures virtually complete elimination of the spectral peak corresponding to the water or the solvent used and allows the use of very high receiver gains.
  • the excitation and acquisition method according to the invention can be used in combination with most high resolution NMR experiments, in particular those mentioned at the beginning of this thesis.
  • the excitation and acquisition method advantageously consists, before emission of the pulse sequence 1 corresponding to the experience of High resolution NMR to be carried out, subjecting the sample to a selective radiofrequency pulse 8 of 90 °, having a carrier frequency identical to the resonant frequency of the solvent, for example water, so that the magnetization of the solvent returns to its equilibrium position under the influence of a second non-selective 8 ° radiofrequency pulse of 90 °.
  • Figure 8a shows the implementation of this additional provision of the invention in the context of a 1D NMR experiment. However, it is also possible to apply this arrangement in combination with other NMR experiments, in particular of the 2D type.
  • This additional arrangement of the invention makes it possible, when the relaxation time is substantially the same value as the relaxation time T1 of the water or of the corresponding solvent, to avoid a partial saturation of the resonance of the water or of the solvent. corresponding, and therefore a saturation and a modification of the signals of the protons exchanged with water or the solvent, these harmful effects possibly possibly also being transferred, via the diffusion of spins to the protons not exchanged with water or the corresponding solvent.
  • the applied 90 ° selective pulse 8 can, for example, consist of a pulse of the type known under the name EBURP 2 (Excitation Band selective Uniform Response Pure phase - selective uniform excitation of pure phase) and described in particular in "Journal of magnetic resonance", 93, 93-141, 1991 by Helen Geen and Ray Freeman.
  • EBURP 2 Excitation Band selective Uniform Response Pure phase - selective uniform excitation of pure phase
  • Such a pulse 8 makes it possible to produce a narrow band excitation of the molecules of water or of corresponding solvent, with a uniform phase over the width of the excitation band and negligible disturbance in the other remaining spectral domains.
  • excitation and acquisition method according to the present invention described above in association with one-dimensional or two-dimensional NMR experiments can, of course, also be implemented in combination or in the context of Three-dimensional or four-dimensional NMR.

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  • Physics & Mathematics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • General Physics & Mathematics (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)
EP93440090A 1992-11-13 1993-11-04 Verfahren zur Anregung und Ermittlung von magnetischen Kernresonanzsignalen, insbesondere in Leichtwasser Expired - Lifetime EP0597785B1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP99102352A EP0913700B1 (de) 1992-11-13 1993-11-04 Verfahren zur Anregung und Aufnahme von magnetischen Kernresonanzsigalen, insbesondere in leichtem Wasser

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR9213825 1992-11-13
FR9213825A FR2698177B1 (fr) 1992-11-13 1992-11-13 Procédé d'excitation et d'acquisition de signaux de résonance magnétique nucléaire, notamment dans l'eau légère.

Related Child Applications (1)

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EP99102352A Division EP0913700B1 (de) 1992-11-13 1993-11-04 Verfahren zur Anregung und Aufnahme von magnetischen Kernresonanzsigalen, insbesondere in leichtem Wasser

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EP0597785A1 true EP0597785A1 (de) 1994-05-18
EP0597785B1 EP0597785B1 (de) 1999-09-29

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EP99102352A Expired - Lifetime EP0913700B1 (de) 1992-11-13 1993-11-04 Verfahren zur Anregung und Aufnahme von magnetischen Kernresonanzsigalen, insbesondere in leichtem Wasser
EP93440090A Expired - Lifetime EP0597785B1 (de) 1992-11-13 1993-11-04 Verfahren zur Anregung und Ermittlung von magnetischen Kernresonanzsignalen, insbesondere in Leichtwasser

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US (1) US5475308A (de)
EP (2) EP0913700B1 (de)
DE (2) DE69326594T2 (de)
FR (1) FR2698177B1 (de)

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US5677628A (en) * 1995-03-15 1997-10-14 Kabushiki Kaisha Toshiba Magnetic resonance diagnostic apparatus
US6005390A (en) * 1995-03-15 1999-12-21 Kabushiki Kaisha Toshiba Magnetic resonance diagnostic apparatus
DE10035319C2 (de) * 2000-07-18 2002-12-05 Universitaetsklinikum Freiburg Verfahren zur Messung der Magnetresonanz (=NMR) mittels Spin-Echos unter Bildung von Hyperechos
CN101356447B (zh) * 2005-07-21 2012-06-27 约翰斯霍普金斯大学 组织糖原的非侵入式mri测定
US8970217B1 (en) 2010-04-14 2015-03-03 Hypres, Inc. System and method for noise reduction in magnetic resonance imaging

Citations (3)

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EP0370333A2 (de) * 1988-11-25 1990-05-30 General Electric Company Bildgebung von Metaboliten mittels magnetischer Kernresonanz mit einer Vielfach-Quantum-Anregungssequenz
EP0460929A2 (de) * 1990-06-07 1991-12-11 General Electric Company NMR Spektroskopie
EP0467467A2 (de) * 1990-07-20 1992-01-22 Philips Patentverwaltung GmbH Kernresonanz-Spektroskopieverfahren

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GB8520587D0 (en) * 1985-08-16 1985-09-25 Picker Int Ltd Spectroscopy method
US4912050A (en) * 1986-02-26 1990-03-27 The Beth Israel Hospital Association Process for the screening of cancer using nuclear magnetic resonance
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EP0370333A2 (de) * 1988-11-25 1990-05-30 General Electric Company Bildgebung von Metaboliten mittels magnetischer Kernresonanz mit einer Vielfach-Quantum-Anregungssequenz
EP0460929A2 (de) * 1990-06-07 1991-12-11 General Electric Company NMR Spektroskopie
EP0467467A2 (de) * 1990-07-20 1992-01-22 Philips Patentverwaltung GmbH Kernresonanz-Spektroskopieverfahren

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A. BAX ET AL.: "OPTIMIZED RECORDING OF HETERONUCLEAR MULTIDIMENSIONAL NMR SPECTRA USING PULSED FIELD GRADIENTS", JOURNAL OF MAGNETIC RESONANCE., vol. 99, no. 3, 1 October 1992 (1992-10-01), ORLANDO, MN US, pages 638 - 643, XP023958986, DOI: doi:10.1016/0022-2364(92)90221-R *
B.K. JOHN ET AL.: "EFFECTIVE COMBINATION OF GRADIENTS AND CRAFTED RF PULSES FOR WATER SUPPRESSION IN BIOLOGICAL SAMPLES", JOURNAL OF MAGNETIC RESONANCE., vol. 98, no. 1, 1 June 1992 (1992-06-01), ORLANDO, MN US, pages 200 - 206, XP023961229, DOI: doi:10.1016/0022-2364(92)90125-Q *
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Publication number Publication date
EP0913700A2 (de) 1999-05-06
FR2698177B1 (fr) 1994-12-30
DE69330766T2 (de) 2002-07-04
DE69326594T2 (de) 2000-05-31
EP0597785B1 (de) 1999-09-29
EP0913700B1 (de) 2001-09-12
DE69330766D1 (de) 2001-10-18
DE69326594D1 (de) 1999-11-04
FR2698177A1 (fr) 1994-05-20
EP0913700A3 (de) 1999-07-21
US5475308A (en) 1995-12-12

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